Normalize leptokurtic quantitative outcome measure in R?
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Entering edit mode
8.6 years ago
dam4l ▴ 200

I have a datafile with 4 columns that looks like this:

fid     iid     phen        sig
0002    0002    -.268465    0
0005    0005    -.033474    0
0081    0081    .2921848    0
0091    0091    1.836548    1
0094    0094    .9888859    1
0095    0095    -.1503887   0

The values in the 'phen' column have a leptokurtic distribution. I want to perform quantile normalization to give them a normal distribution.

I read the data into R using data <- read.table('phenfile.txt'). The 'cape' package (norm.pheno function) gives back an error message (dim(X) must have a positive length) and the 'preprocessCore' package (using normalize.quantiles(as.matrix(data[,"phen", drop = FALSE]))) failed to normalize the distribution.

Are there any other packages/functions in R that could be used to normalize a single column of values within a document?

Any input would be greatly appreciated.

r gwas SNP • 2.1k views
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Entering edit mode
8.6 years ago
Michael 55k

See Crossvalidated for the problem of conversion: https://stats.stackexchange.com/questions/85687/how-to-transform-leptokurtic-distribution-to-normality

You first should make a QQ-plot to analyze the deviation from normal. You need to apply a transformation, not a normalization. A transformation can be any function, like logarithm (for an exponential variable), sqrt, etc.

Regarding quantile normalization:

  • quantile normalization is not the right tool
  • quantile normalization cannot be applied to a single column, it would not change anything at best
  • quantile normalization does not make the data more like a normal distribution, instead it makes that all values of all columns are sampled from the same values, or effectively that each column is a different permutation of the same set of values.
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I plotted the values in the 'phen' column in a histogram to see the distribution - skewness was okay but it was leptokurtic. I'm using the values in 'phen' in a linear regression. The resulting p-vals from the regression are not normally distributed (I plotted them on -log(p) transformed QQ plot). After looking at the post you linked to, I'm still not sure what the best way to normalize the distribution of the 'phen' column would be.

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p-values are not expected to be normal, under the true null hypotheses they should be uniformly distributed, e.g.: 1% with p<0.01, 5% with p<0.05, for any p etc. uniform is the only distribution satisfying this. (see https://stats.stackexchange.com/questions/10613/why-are-p-values-uniformly-distributed-under-the-null-hypothesis )

You need to make a QQ plot of the data (phen), not the p-values.

The answer on Crossv. states that it might not be always exist a closed form transformation to make a non-normal variable normal. The second answer points to possible transformation. If you want to go into the guts of the statistics behind, you should rather ask this Q on Crossvalidated.

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